Kim Jun-Dal, Kako Koichiro, Kakiuchi Misako, Park Gwi Gun, Fukamizu Akiyoshi
Graduate School of Life & Environmental Science, University of Tsukuba, Tsukuba, Ibaraki 305-8572, Japan.
Int J Mol Med. 2008 Sep;22(3):309-15.
EWS, a pro-oncoprotein which is encoded by the Ewing sarcoma (EWS) gene, contains arginine-glycine-glycine repeats (RGG box) in its COOH-terminus. We previously found that the RGG box of EWS is a target for dimethylation catalyzed by protein arginine methyltransferases (PRMTs). Although it has been observed that arginine residues in EWS are dimethylated in vivo, the endogenous enzyme(s) responsible for this reaction have not been identified to date. In the present study, we determined that EWS was physically associated with PRMT8, the novel eighth member of the PRMT family, through the COOH-terminal region of EWS including RGG3 with the NH2-terminal region of PRMT8 encompassing the S-adenosyl-L-methionine binding domain, and that arginine residues in EWS were asymmetrically dimethylated by PRMT8 using amino acid analysis with thin-layer chromatography. These results suggested that EWS is a substrate for PRMT8, as efficient as for PRMT1.
EWS是一种由尤因肉瘤（EWS）基因编码的原癌蛋白，其COOH末端含有精氨酸-甘氨酸-甘氨酸重复序列（RGG框）。我们之前发现EWS的RGG框是蛋白质精氨酸甲基转移酶（PRMTs）催化二甲基化的靶点。尽管已经观察到EWS中的精氨酸残基在体内会发生二甲基化，但迄今为止尚未鉴定出负责该反应的内源性酶。在本研究中，我们确定EWS通过EWS的COOH末端区域（包括RGG3）与PRMT家族的新成员PRMT8的NH2末端区域（包含S-腺苷-L-甲硫氨酸结合域）发生物理相互作用，并且通过薄层色谱氨基酸分析表明EWS中的精氨酸残基被PRMT8不对称二甲基化。这些结果表明EWS是PRMT8的底物，其效率与PRMT1相同。
